Theoretical study of the deposition and adsorption of bisphosphonates on the 001 hydroxyapatite surface: Implications in the pathological crystallization inhibition and the bone antiresorptive action

Abstract The effect of different side chain groups of bisphosphonates (BPs) on the adsorption on the hydroxyapatite (HAP) is still a controversial issue. In this work, we studied the deposition and adsorption of a set of 26 BPs on the HAP (001) surface by using density functional theory (DFT) in which has been shown that the charge, the length or the presence of different functional groups at R 2 side chain can modulate the adsorption energy of the BP. It was observed that negative charged groups at R 2 enhanced the favourable electrostatic interactions between the BP and the HAP surface, but also that the length of R 2 was important to enable the formation of the favorable electrostatic interactions between the functional group at R 2 and the surface. A crossover study between the HAP/BP model (3D-QSAR/DFT) and the inhibition of the human farnesyl pyrophosphate synthase (FPPS) (3D-QSAR) pointed out that the electrostatic character of the R 2 side chain provokes contrary effects in the inhibition of pathological crystallization and in the bone antiresorptive action of BPs.